Morphometric and Nanomechanical Features of Erythrocytes Characteristic of Early Pregnancy Loss

Early pregnancy loss (EPL) is estimated to be between 15 and 20% of all adverse pregnancies. Approximately, half of EPL cases have no identifiable cause. Herein, we apply atomic force microscopy to evaluate the alteration of morphology and nanomechanics of erythrocytes from women with EPL with unknown etiology, as compared to healthy pregnant (PC) and nonpregnant women (NPC). Freshly isolated erythrocytes from women with EPL differ in both the roughness value (4.6 ± 0.3 nm, p < 0.05), and Young’s modulus (2.54 ± 0.6 MPa, p < 0.01) compared to the values for NPC (3.8 ± 0.4 nm and 0.94 ± 0.2 MPa, respectively) and PC (3.3 ± 0.2 nm and 1.12 ± 0.3 MPa, respectively). Moreover, we find a time-dependent trend for the reduction of the cells’ morphometric parameters (cells size and surface roughness) and the membrane elasticity—much faster for EPL than for the two control groups. The accelerated aging of EPL erythrocytes is expressed in faster morphological shape transformation and earlier occurrence of spiculated and spherical-shaped cells, reduced membrane roughness and elasticity with aging evolution. Oxidative stress in vitro contributed to the morphological cells’ changes observed for EPL senescent erythrocytes. The ultrastructural characteristics of cells derived from women with miscarriages show potential as a supplementary mark for a pathological state.     

Fabrication of self-assembled Au droplets by the systematic variation of the deposition amount on various type-B GaAs surfaces

The fabrication of self-assembled Au droplets is successfully demonstrated on various GaAs (n11)B, where n is 2, 4, 5, 7, 8, and 9, by the systematic variation of the Au deposition amount (DA) from 2 to 12 nm with subsequent annealing at 550°C. Under an identical growth condition, the self-assembled Au droplets of mini to supersizes are successfully synthesized via the Volmer-Weber growth mode. Depending on the DA, an apparent evolution is clearly observed in terms of the average height (AH), lateral diameter (LD), and average density (AD). For example, compared with the mini Au droplets with a DA of 2 nm, AH of 22.5 nm, and LD of 86.5 nm, the super Au droplets with 12-nm DA show significantly increased AH of 316% and LD of 320%, reaching an AH of 71.1 nm and LD of 276.8 nm on GaAs (211)B. In addition, accompanied with the dimensional expansion, the AD of Au droplets drastically swings on 2 orders of magnitudes from 3.2 × 10¹⁰ to 4.2 × 10⁸ cm^-2. The results are systematically analyzed with respect to the atomic force microscopy (AFM) and scanning electron microscopy (SEM) images, energy-dispersive X-ray spectrometry (EDS) spectra, cross-sectional line profiles, Fourier filter transform (FFT) power spectra, and root-mean-square (RMS) roughness as well as the droplet dimension and density summary, respectively.     

Inhibitory Mechanisms of Lusianthridin on Human Platelet Aggregation

Lusianthridin is a phenanthrene derivative isolated from Dendrobium venustum. Some phenanthrene compounds have antiplatelet aggregation activities via undefined pathways. This study aims to determine the inhibitory effects and potential mechanisms of lusianthridin on platelet aggregation. The results indicated that lusianthridin inhibited arachidonic acid, collagen, and adenosine diphosphate (ADP)-stimulated platelet aggregation (IC₅₀ of 0.02 ± 0.001 mM, 0.14 ± 0.018 mM, and 0.22 ± 0.046 mM, respectively). Lusianthridin also increased the delaying time of arachidonic acid-stimulated and the lag time of collagen-stimulated and showed a more selective effect on the secondary wave of ADP-stimulated aggregations. Molecular docking studies revealed that lusianthridin bound to the entrance site of the cyclooxygenase-1 (COX-1) enzyme and probably the active region of the cyclooxygenase-2 (COX-2) enzyme. In addition, lusianthridin showed inhibitory effects on both COX-1 and COX-2 enzymatic activities (IC₅₀ value of 10.81 ± 1.12 µM and 0.17 ± 1.62 µM, respectively). Furthermore, lusianthridin significantly inhibited ADP-induced suppression of cAMP formation in platelets at 0.4 mM concentration (p < 0.05). These findings suggested that possible mechanisms of lusianthridin on the antiplatelet effects might act via arachidonic acid-thromboxane and adenylate cyclase pathways.     

Development of MRI-Detectable Boron-Containing Gold Nanoparticle-Encapsulated Biodegradable Polymeric Matrix for Boron Neutron Capture Therapy (BNCT)

This study aimed to develop a novel magnetic resonance imaging (MRI)-detectable boron (B)-containing nanoassemblies and evaluate their potential for boron neutron capture therapy (BNCT). Starting from the citrate-coated gold nanoparticles (AuNPs) (23.9 ± 10.2 nm), the diameter of poly (D, L-lactide-co-glycolide) AuNPs (PLGA-AuNPs) increased approximately 110 nm after the encapsulation of the PLGA polymer. Among various B drugs, the self-produced B cages had the highest loading efficiency. The average diameter of gadolinium (Gd)- and B-loaded NPs (PLGA-Gd/B-AuNPs) was 160.6 ± 50.6 nm with a B encapsulation efficiency of 28.7 ± 2.3%. In vitro MR images showed that the signal intensity of PLGA-Gd/B-AuNPs in T1-weighted images was proportional to its Gd concentration, and there exists a significantly positive relationship between Gd and B concentrations (R² = 0.74, p < 0.005). The hyperintensity of either 250 ± 50 mm³ (larger) or 100 ± 50 mm³ (smaller) N87 xenograft was clearly visualized at 1 h after intravenous injection of PLGA-Gd/B-AuNPs. However, PLGA-Gd/B-AuNPs stayed at the periphery of the larger xenograft while located near the center of the smaller one. The tumor-to-muscle ratios of B content, determined by inductively coupled plasma mass spectrometry, in smaller- and larger-sized tumors were 4.17 ± 1.42 and 1.99 ± 0.55, respectively. In summary, we successfully developed theranostic B- and Gd-containing AuNPs for BNCT in this study.     

Platelet Inhibition Prevents NLRP3 Inflammasome Activation and Sepsis-Induced Kidney Injury

Platelets, cellular mediators of thrombosis, are activated during sepsis and are increasingly recognized as mediators of the immune response. Platelet activation is significantly increased in sepsis patients compared to ICU control patients. Despite this correlation, the role of activated platelets in contributing to sepsis pathophysiology remains unclear. We previously demonstrated NOD-like receptor protein 3 inflammasome (NLRP3) inflammasome activation in sepsis-induced platelets from cecal-ligation puncture (CLP) rats. Activated platelets were associated with increased pulmonary edema and glomerular injury in CLP vs. SHAM controls. In this study, we investigated whether inhibition of platelet activation would attenuate NLRP3 activation and renal and pulmonary injury in response to CLP. CLP was performed in male and female Sprague Dawley (SD) rats (n = 10/group) to induce abdominal sepsis and SHAM rats served as controls. A subset of CLP animals was treated with Clopidogrel (10 mg/kg/day, CLP + CLOP) to inhibit platelet activation. At 72 h post-CLP, platelet activation and NLRP3 inflammasome assembly were evaluated, IL-1β and IL-18 were measured in plasma, and tissues, renal and pulmonary pathology, and renal function were assessed. Activated platelets were 7.8 ± 3.6% in Sham, 22 ± 6% in CLP and significantly decreased to 14.5 ± 0.6% in CLP + CLOP (n = 8–10/group, p < 0.05). NLRP3 inflammasome assembly was inhibited in platelets of CLP + CLOP animals vs. CLP. Significant increases in plasma and kidney IL-1β and IL-18 in response to CLP were decreased with Clopidogrel treatment. Renal injury, but not lung histology or renal function was improved in CLP + CLOP vs. CLP. These data provide evidence that activated platelets may contribute to sepsis-induced renal injury, possibly via NLRP3 activation in platelets. Platelets may be a therapeutic target to decrease renal injury in septic patients.     

Altered Thermal Behavior of Blood Plasma Proteome Related to Inflammatory Cytokines in Early Pregnancy Loss

Early pregnancy loss (EPL) is a relatively common pathology of which almost 50% of cases remain idiopathic. In the search for novel biomarkers, differential scanning calorimetry (DSC) is intensively used to characterize the thermodynamic behavior of blood plasma/serum proteome in health and disease. Herein, for the first time, we investigate the DSC denaturation profiles of blood plasma derived from patients suffering EPL compared to healthy pregnant and non-pregnant women. Data analysis reveals that 58% of the EPL thermograms differ significantly from those of healthy pregnant women. Thermal stabilization of a fraction of albumin-assigned transition with concomitant suppression of the major and enhancement of the globulin-assigned transition are characteristic features of EPL calorimetric profiles that could be used as a new indicator of a risk pregnancy. The presented results suggest an altered composition or intermolecular interactions of the plasma proteome of women with EPL. In addition, the alterations of the EPL thermograms correlate with the increased blood levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) and a higher prevalence of the polymorphism in the plasminogen activator inhibitor type-1 (PAI-1) gene, suggesting an expression of an overall enhanced immune response. The concomitant changes in plasma thermograms confirm the potential of the DSC approach for distinguishing changes in the pathological state of the blood plasma proteome.     

Long-Term Vitamin D Deficiency Results in the Inhibition of Cell Proliferation and Alteration of Multiple Gastric Epithelial Cell Lineages in Mice

Over one billion people globally are vitamin D (VD) deficient. Studies on the biological roles of VD are numerous but very little on the stomach. This project aims to understand how gastric homeostasis is affected by VD deficiency caused by prolonged exposure to darkness alone or combined with VD deficient diet. Three groups of C57/BL6 mice were subjected to different light exposure conditions and diets for 12 months (n = 8–12/group): control—12 h/12 h light/dark SDL (Standard Diet/Light), 24 h dark SDD (Standard Diet/Dark), and 24 h dark VDD (VD deficient diet/Dark). Stomach samples were collected for different multi-label lectin-/immuno-histochemical and qRT-PCR analyses, and the serum for LC-MS-MS. We found that the membrane VD receptor is expressed widely in the stomach when compared to nuclear VD receptors. Compared to SDL, VDD mice developed mucous cell expansion with increased mucins-mRNA (3.27 ± 2.73 (p < 0.05)) increased apoptotic cells, 15 ± 7 (p ≤ 0.001)); decreased cell proliferation, 4 ± 4 (p < 0.05)) and decreased acid secretion 33 ± 2 μEq/kg (p ≤ 0.0001)). Interestingly, mice exposed to full darkness developed mild VD deficiency with higher VD epimer levels: 11.9 ± 2.08 ng/mL (p ≤ 0.0001)), expansion in zymogenic cell number (16 ± 3 (p ≤ 0.01)), and a reduction in acid secretion (18 ± 2 μEq/kg (p ≤ 0.0001)). In conclusion, changes in light exposure or VD levels have serious physiological effects on the gastric mucosa, which should be considered during the management of gastric disorders.     

An Eco-Friendly Approach to the Control of Pathogenic Microbes and Anopheles stephensi Malarial Vector Using Magnesium Oxide Nanoparticles (Mg-NPs) Fabricated by Penicillium chrysogenum

The discovery of eco-friendly, rapid, and cost-effective compounds to control diseases caused by microbes and insects are the main challenges. Herein, the magnesium oxide nanoparticles (MgO-NPs) are successfully fabricated by harnessing the metabolites secreted by Penicillium chrysogenum. The fabricated MgO-NPs were characterized using UV-Vis, XRD, TEM, DLS, EDX, FT-IR, and XPS analyses. Data showed the successful formation of crystallographic, spherical, well-dispersed MgO-NPs with sizes of 7–40 nm at a maximum wavelength of 250 nm. The EDX analysis confirms the presence of Mg and O ions as the main components with weight percentages of 13.62% and 7.76%, respectively. The activity of MgO-NPs as an antimicrobial agent was investigated against pathogens Staphylococcus aureus, Bacillus subtilis, Pseudomonas aeruginosa, Escherichia coli, and Candida albicans, and exhibited zone of inhibitions of 12.0 ± 0.0, 12.7 ± 0.9, 23.3 ± 0.8, 17.7 ± 1.6, and 14.7 ± 0.6 mm respectively, at 200 µg mL⁻¹. The activity is decreased by decreasing the MgO-NPs concentration. The biogenic MgO-NPs exhibit high efficacy against different larvae instar and pupa of Anopheles stephensi, with LC50 values of 12.5–15.5 ppm for I–IV larvae instar and 16.5 ppm for the pupa. Additionally, 5 mg/cm² of MgO-NPs showed the highest protection percentages against adults of Anopheles stephensi, with values of 100% for 150 min and 67.6% ± 1.4% for 210 min.     

Study and characterization of porous copper oxide produced by electrochemical anodization for radiometric heat absorber

The aim of this work is to optimize the different parameters for realization of an absorbing cavity to measure the incident absolute laser energy. Electrochemical oxidation is the background process that allowed the copper blackening. A study of the blackened surface quality was undertaken using atomic force microscopy (AFM) analysis and ultraviolet-visible-infrared spectrophotometry using a Shimadzu spectrophotometer. A two-dimensional and three-dimensional visualization by AFM of the formed oxide coating showed that the copper surfaces became porous after electrochemical etching with different roughness. This aspect is becoming more and more important with decreasing current density anodization. In a 2 mol L ^-1 of NaOH solution, at a temperature of 90°C, and using a 16 mA cm² constant density current, the copper oxide formed has a reflectivity of around 3% in the spectral range between 300 and 1,800 nm. Using the ‘mirage effect’ technique, the obtained Cu₂O diffusivity and thermal conductivity are respectively equal to (11.5 ± 0.5) 10 to 7 m² s^-1 and (370 ± 20) Wm^-1 K^-1. This allows us to consider that our Cu₂O coating is a good thermal conductor. The results of the optical and thermal studies dictate the choice of the cavity design. The absorbing cavity is a hollow cylinder machined to its base at an angle of 30°. If the included angle of the plane is 30° and the interior surface gives specular reflection, an incoming ray parallel to the axis will undergo five reflections before exit. So the absorption of the surface becomes closely near 0.999999.     

Worsening of the Toxic Effects of (±)Cis-4,4′-DMAR Following Its Co-Administration with (±)Trans-4,4′-DMAR: Neuro-Behavioural,Physiological, Immunohistochemical and Metabolic Studies in Mice

4,4’-Dimethylaminorex (4,4’-DMAR) is a new synthetic stimulant, and only a little information has been made available so far regarding its pharmaco-toxicological effects. The aim of this study was to investigate the effects of the systemic administration of both the single (±)cis (0.1–60 mg/kg) and (±)trans (30 and 60 mg/kg) stereoisomers and their co-administration (e.g., (±)cis at 1, 10 or 60 mg/kg + (±)trans at 30 mg/kg) in mice. Moreover, we investigated the effect of 4,4′-DMAR on the expression of markers of oxidative/nitrosative stress (8-OHdG, iNOS, NT and NOX2), apoptosis (Smac/DIABLO and NF-κB), and heat shock proteins (HSP27, HSP70, HSP90) in the cerebral cortex. Our study demonstrated that the (±)cis stereoisomer dose-dependently induced psychomotor agitation, sweating, salivation, hyperthermia, stimulated aggression, convulsions and death. Conversely, the (±)trans stereoisomer was ineffective whilst the stereoisomers’ co-administration resulted in a worsening of the toxic (±)cis stereoisomer effects. This trend of responses was confirmed by immunohistochemical analysis on the cortex. Finally, we investigated the potentially toxic effects of stereoisomer co-administration by studying urinary excretion. The excretion study showed that the (±)trans stereoisomer reduced the metabolism of the (±)cis form and increased its amount in the urine, possibly reflecting its increased plasma levels and, therefore, the worsening of its toxicity.     

Self-organizing nanodot structures on InP surfaces evolving under low-energy ion irradiation: analysis of morphology and composition

Surfaces of InP were bombarded by 1.9 keV Ar⁺ ions under normal incidence. The total accumulated ion fluence Φ the samples were exposed to was varied from 1 × 10¹⁷ cm⁻² to 3 × 10¹⁸ cm⁻², and ion fluxes f of (0.4 − 2) × 10¹⁴ cm⁻² s⁻¹ were used. The surface morphology resulting from these ion irradiations was examined by atomic force microscopy (AFM). Generally, nanodot structures are formed on the surface; their dimensions (diameter, height and separation), however, were found to depend critically on the specific bombardment conditions. As a function of ion fluence, the mean radius r, height h, and spacing l of the dots can be fitted by power-law dependences: r ∝ Φ^0.40, h ∝ Φ^0.48, and l ∝ Φ^0.19. In terms of ion flux, there appears to exist a distinct threshold: below f ~ (1.3 ± 0.2) × 10¹⁴ cm⁻² s⁻¹, no ordering of the dots exists and their size is comparatively small; above that value of f, the height and radius of the dots becomes substantially larger (h ~ 40 nm and r ~ 50 nm). This finding possibly indicates that surface diffusion processes could be important. In order to determine possible local compositional changes in these nanostructures induced by ion impact, selected samples were prepared for atom probe tomography (APT). The results indicate that APT can provide analytical information on the composition of individual InP nanodots. By means of 3D APT data, the surface region of such nanodots evolving under ion bombardment could be examined with atomic spatial resolution. At the InP surface, the values of the In/P concentration ratio are distinctly higher over a distance of approximately 1 nm and amount to 1.3 to 1.7.     

Microwave-assisted synthesis of layered basic zinc acetate nanosheets and their thermal decomposition into nanocrystalline ZnO

We have developed a low-cost technique using a conventional microwave oven to grow layered basic zinc acetate (LBZA) nanosheets (NSs) from a zinc acetate, zinc nitrate and HMTA solution in only 2 min. The as-grown crystals and their pyrolytic decomposition into ZnO nanocrystalline NSs are characterized by scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDS), atomic force microscopy (AFM), X-ray diffraction (XRD) and photoluminescence (PL). SEM and AFM measurements show that the LBZA NSs have typical lateral dimensions of 1 to 5 μm and thickness of 20 to 100 nm. Annealing in air from 200°C to 1,000°C results in the formation of ZnO nanocrystalline NSs, with a nanocrystallite size ranging from 16 nm at 200°C to 104 nm at 1,000°C, as determined by SEM. SEM shows evidence of sintering at 600°C. PL shows that the shape of the visible band is greatly affected by the annealing temperature and that the exciton band to defect band intensity ratio is maximum at 400°C and decreases by a factor of 15 after annealing at 600°C. The shape and thickness of the ZnO nanocrystalline NSs are the same as LBZA NSs. This structure provides a high surface-to-volume ratio of interconnected nanoparticles that is favorable for applications requiring high specific area and low resistivity such as gas sensing and dye-sensitized solar cells (DSCs). We show that resistive gas sensors fabricated with the ZnO NSs showed a response of 1.12 and 1.65 to 12.5 ppm and 200 ppm of CO at 350°C in dry air, respectively, and that DSCs also fabricated from the material had an overall efficiency of 1.3%.

PACS

81.07.-b; 62.23.Kn; 61.82.Fk     

Does Melatonin Homeostasis Play a Role in Continuous Epigastric Pain Syndrome?

Two clinical forms of functional dyspepsia (FD) are listed in the Rome III criteria: postprandial distress syndrome (PDS) and epigastric pain syndrome (EPS), differing in the recurrence of ailments depending on the diet. Continuous EPS (CEPS) is observed in some EPS patients, also at night, but its cause is still unknown. We showed previously that melatonin (MEL) homeostasis may be associated with FD. In the present work we evaluated selected components of melatonin homeostasis in patients with CEPS. The study included 30 patients with CEPS, 21 women and nine men, aged 21–49 years and 30 control subjects (EPS excluded); organic and mental diseases, as well as Helicobacter pylori infection, were excluded in both groups. The average severity of abdominal pain in the last three months was estimated in a 10-point scale (Visual Analog Scale). The levels of mRNA expression of arylalkylamine-N-acetyltransferase (AANAT) and hydroxyindole-O-methyltransferase (HIOMT), the main components of MEL homeostasis, were determined in gastric mucosa with real time PCR. The fasting serum level of MEL (at 09:00 a.m.) and circadian urine excretion of 6-sulfatoxymelatonin (6-HMS) were determined with ELISA. AANAT expression in antral mucosa of control subjects was 1.76 ± 0.41, in the gastric body 1.35 ± 0.38, and in the dyspeptic group 1.42 ± 0.38 (p < 0.05) and 0.92 ± 0.55 (p < 0.05), respectively. HIOMT expression in the control was 2.05 ± 0.70 in the antrum and 1.57 ± 0.69 in the body and in the CEPS group, it was: 1.51 ± 0.57 (p < 0.05) and 0.74 ± 0.31 (p < 0.001), respectively. MEL concentration (pg/mL) was 9.41 ± 3.09 in the control group and 5.62 ± 1.34 (p < 0.01) in the CEPS group. Urinary 6-HMS excretion (μg/24 h) was 11.40 ± 4.46 in the controls and 7.68 ± 2.88 (p < 0.05) in the CEPS. Moreover, a negative correlation was found between the tested parameters and severity of epigastric pain. These results indicate that patients with CEPS may display low level of AANAT and HIOMT expression in gastric mucosa, resulting in decreased MEL synthesis.     

In Vitro Activity of Copper(II) Complexes,Loaded or Unloaded into a Nanostructured Lipid System,against Mycobacterium tuberculosis

Tuberculosis (TB) is an infectious disease caused mainly by the bacillus Mycobacterium tuberculosis (Mtb), presenting 9.5 million new cases and 1.5 million deaths in 2014. The aim of this study was to evaluate a nanostructured lipid system (NLS) composed of 10% phase oil (cholesterol), 10% surfactant (soy phosphatidylcholine, sodium oleate), and Eumulgin^® HRE 40 ([castor oil polyoxyl-40-hydrogenated] in a proportion of 3:6:8), and an 80% aqueous phase (phosphate buffer pH = 7.4) as a tactic to enhance the in vitro anti-Mtb activity of the copper(II) complexes [CuCl₂(INH)₂]·H₂O (1), [Cu(NCS)₂(INH)₂]·5H₂O (2) and [Cu(NCO)₂(INH)₂]·4H₂O (3). The Cu(II) complex-loaded NLS displayed sizes ranging from 169.5 ± 0.7095 to 211.1 ± 0.8963 nm, polydispersity index (PDI) varying from 0.135 ± 0.0130 to 0.236 ± 0.00100, and zeta potential ranging from −0.00690 ± 0.0896 to −8.43 ± 1.63 mV. Rheological analysis showed that the formulations behave as non-Newtonian fluids of the pseudoplastic and viscoelastic type. Antimycobacterial activities of the free complexes and NLS-loaded complexes against Mtb H₃₇Rv ATCC 27294 were evaluated by the REMA methodology, and the selectivity index (SI) was calculated using the cytotoxicity index (IC₅₀) against Vero (ATCC^® CCL-81), J774A.1 (ATCC^® TIB-67), and MRC-5 (ATCC^® CCL-171) cell lines. The data suggest that the incorporation of the complexes into NLS improved the inhibitory action against Mtb by 52-, 27-, and 4.7-fold and the SI values by 173-, 43-, and 7-fold for the compounds 1, 2 and 3, respectively. The incorporation of the complexes 1, 2 and 3 into the NLS also resulted in a significant decrease of toxicity towards an alternative model (Artemia salina L.). These findings suggest that the NLS may be considered as a platform for incorporation of metallic complexes aimed at the treatment of TB.     

Effects of Melatonin on the Proliferation and Apoptosis of Sheep Granulosa Cells under Thermal Stress

The cross-talk between oocyte and somatic cells plays a crucial role in the regulation of follicular development and oocyte maturation. As a result, granulosa cell apoptosis causes follicular atresia. In this study, sheep granulosa cells were cultured under thermal stress to induce apoptosis, and melatonin (MT) was examined to evaluate its potential effects on heat-induced granulosa cell injury. The results demonstrated that the Colony Forming Efficiency (CFE) of granulosa cells was significantly decreased (heat 19.70% ± 1.29% vs. control 26.96% ± 1.81%, p < 0.05) and the apoptosis rate was significantly increased (heat 56.16% ± 13.95%vs. control 22.80% ± 12.16%, p < 0.05) in granulosa cells with thermal stress compared with the control group. Melatonin (10⁻⁷ M) remarkably reduced the negative effects caused by thermal stress in the granulosa cells. This reduction was indicated by the improved CFE and decreased apoptotic rate of these cells. The beneficial effects of melatonin on thermal stressed granulosa cells were not inhibited by its membrane receptor antagonist luzindole. A mechanistic exploration indicated that melatonin (10⁻⁷ M) down-regulated p53 and up-regulated Bcl-2 and LHR gene expression of granulosa cells under thermal stress. This study provides evidence for the molecular mechanisms of the protective effects of melatonin on granulosa cells during thermal stress.     

Melatonin as a Signaling Molecule for Metabolism Regulation in Response to Hypoxia in the Crab Neohelice granulata

Melatonin has been identified in a variety of crustacean species, but its function is not as well understood as in vertebrates. The present study investigates whether melatonin has an effect on crustacean hyperglycemic hormone (CHH) gene expression, oxygen consumption (VO₂) and circulating glucose and lactate levels, in response to different dissolved-oxygen concentrations, in the crab Neohelice granulata, as well as whether these possible effects are eyestalk- or receptor-dependent. Melatonin decreased CHH expression in crabs exposed for 45 min to 6 (2, 200 or 20,000 pmol·crab⁻¹) or 2 mgO₂·L⁻¹ (200 pmol·crab⁻¹). Since luzindole (200 nmol·crab⁻¹) did not significantly (p > 0.05) alter the melatonin effect, its action does not seem to be mediated by vertebrate-typical MT1 and MT2 receptors. Melatonin (200 pmol·crab⁻¹) increased the levels of glucose and lactate in crabs exposed to 6 mgO₂·L⁻¹, and luzindole (200 nmol·crab⁻¹) decreased this effect, indicating that melatonin receptors are involved in hyperglycemia and lactemia. Melatonin showed no effect on VO₂. Interestingly, in vitro incubation of eyestalk ganglia for 45 min at 0.7 mgO₂·L⁻¹ significantly (p < 0.05) increased melatonin production in this organ. In addition, injections of melatonin significantly increased the levels of circulating melatonin in crabs exposed for 45 min to 6 (200 or 20,000 pmol·crab⁻¹), 2 (200 and 20,000 pmol·crab⁻¹) and 0.7 (200 or 20,000 pmol·crab⁻¹) mgO₂·L⁻¹. Therefore, melatonin seems to have an effect on the metabolism of N. granulata. This molecule inhibited the gene expression of CHH and caused an eyestalk- and receptor-dependent hyperglycemia, which suggests that melatonin may have a signaling role in metabolic regulation in this crab.     

Hepatocyte-Specific Deficiency of BAP31 Amplified Acetaminophen-Induced Hepatotoxicity via Attenuating Nrf2 Signaling Activation in Mice

Liver-specific deficiency of B-cell receptor-associated protein 31 knockout mice (BAP31-LKO) and the littermates were injected with acetaminophen (APAP), markers of liver injury, and the potential molecular mechanisms were determined. In response to APAP overdose, serum aspartate aminotransferase and alanine aminotransferase levels were increased in BAP31-LKO mice than in wild-type controls, accompanied by enhanced liver necrosis. APAP-induced apoptosis and mortality were increased. Hepatic glutathione was decreased (1.60 ± 0.31 μmol/g tissue in WT mice vs. 0.85 ± 0.14 μmol/g tissue in BAP31-LKO mice at 6 h, p < 0.05), along with reduced glutathione reductase activity and superoxide dismutase; while malondialdehyde was significantly induced (0.41 ± 0.03 nmol/mg tissue in WT mice vs. 0.50 ± 0.05 nmol/mg tissue in BAP31-LKO mice for 6 h, p < 0.05). JNK signaling activation and APAP-induced hepatic inflammation were increased in BAP31-LKO mice. The mechanism research revealed that BAP31-deficiency decreased Nrf2 mRNA stability (half-life of Nrf2 mRNA decreased from ~1.3 h to ~40 min) and miR-223 expression, led to reduced nuclear factor erythroid 2-related factor 2 (Nrf2) signaling activation and antioxidant genes induction. BAP31-deficiency decreased mitochondrial membrane potentials, reduced mitochondria-related genes expression, and resulted in mitochondrial dysfunction in the liver. Conclusions: BAP31-deficiency reduced the antioxidant response and Nrf2 signaling activation via reducing Nrf2 mRNA stabilization, enhanced JNK signaling activation, hepatic inflammation, and apoptosis, amplified APAP-induced hepatotoxicity in mice.     

Bismuth-induced effects on optical,lattice vibrational,and structural properties of bulk GaAsBi alloys

Bulk GaAs_{1 - x}Bi_x/GaAs alloys with various bismuth compositions are studied using power- and temperature-dependent photoluminescence (PL), Raman scattering, and atomic force microscopy (AFM). PL measurements exhibit that the bandgap of the alloy decreases with increasing bismuth composition. Moreover, PL peak energy and PL characteristic are found to be excitation intensity dependent. The PL signal is detectable below 150 K at low excitation intensities, but quenches at higher temperatures. As excitation intensity is increased, PL can be observable at room temperature and PL peak energy blueshifts. The quenching temperature of the PL signal tends to shift to higher temperatures with increasing bismuth composition, giving rise to an increase in Bi-related localization energy of disorders. The composition dependence of the PL is also found to be power dependent, changing from about 63 to 87 meV/Bi% as excitation intensity is increased. In addition, S-shaped temperature dependence at low excitation intensities is observed, a well-known signature of localized levels above valence band. Applying Varshni’s law to the temperature dependence of the PL peak energy, the concentration dependence of Debye temperature (β) and thermal expansion coefficient (α) are determined. AFM observations show that bismuth islands are randomly distributed on the surface and the diameter of the islands tends to increase with increasing bismuth composition. Raman scattering spectra show that incorporation of Bi into GaAs causes a new feature at around 185 cm^-1 with slightly increasing Raman intensity as the Bi concentration increases. A broad feature located between 210 and 250 cm^-1 is also observed and its intensity increases with increasing Bi content. Furthermore, the forbidden transverse optical (TO) mode becomes more pronounced for the samples with higher bismuth composition, which can be attributed to the effect of Bi-induced disorders on crystal symmetry.

PACS

78.55Cr 78.55-m 78.20-e 78.30-j